Self-Regulation of Candida albicans Population Size during GI Colonization 英文参考文献.docVIP

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Self-Regulation of Candida albicans Population Size during GI Colonization 英文参考文献.doc

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Self-Regulation of Candida albicans Population Size during GI Colonization 英文参考文献

Self-RegulationofCandidaalbicans PopulationSizeduringGIColonization Sarah Jane White1¤a,Ari Rosenbach1,Paul Lephart1¤b,Diem Nguyen1,Alana Benjamin1¤c,Saul Tzipori2, Malcolm Whiteway3,Joan Mecsas1,Carol A.Kumamoto1* 1DepartmentofMolecularBiologyandMicrobiology,TuftsUniversity,Boston,Massachusetts,UnitedStatesofAmerica,2DivisionofInfectiousDiseases,TuftsUniversity, Grafton,Massachusetts,UnitedStatesofAmerica,3GeneticsGroup,BiotechnologyResearchInstitute,NationalResearchCouncil,Montreal,Quebec,Canada Interactions between colonizing commensal microorganisms and their hosts play important roles in health and disease. The opportunistic fungal pathogen Candida albicans is a common component of human intestinal flora. To gaininsightintoC.albicanscolonization,genesexpressedbyfungigrownwithinahostwerestudied.TheEFH1gene, encoding a putative transcription factor, was highly expressed during growth of C. albicans in the intestinal tract. Counterintuitively, an efh1 null mutant exhibited increased colonization of the murine intestinal tract, a model of commensalcolonization,whereasanEFH1overexpressingstrainexhibitedreducedcolonizationoftheintestinaltract andoftheoralcavityofathymicmice,thelattersituationmodelinghumanmucosalcandidiasis.Wheninoculatedinto thebloodstreamofmice,bothefh1nullandEFH1overexpressingstrainscausedlethalinfections.Incontrast,other mutants are attenuated in virulence following intravenous inoculation but exhibited normal levels of intestinal colonization. Finally, although expression of several genes is dependent on transcription factor Efg1p during laboratory growth, Efg1p-independent expression of these genes was observed during growth within the murine intestinal tract. These results show that expression of EFH1 regulated the level of colonizing fungi, favoring commensalismasopposedtocandidiasis.Also,differentgenesarerequiredindifferenthostnichesandthepathway(s) that regulates gene expression during host colonization can differ from well-characterized